Patient Centered AUC-Monitoring of Tacrolimus Using Capillary Microsampling
Oslo University Hospital, Rikshospitalet, Oslo, Norway
Meeting: 2019 American Transplant Congress
Abstract number: 526
Keywords: Immunosuppression, Kidney transplantation, Monitoring
Session Name: Concurrent Session: Kidney Immunosuppression: Novel Regimens and Drug Minimization III
Session Type: Concurrent Session
Date: Tuesday, June 4, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: Veterans Auditorium
*Purpose: To reduce unwanted side effects of Tacrolimus (Tac), improvement of dosing is warranted. Therapeutic drug monitoring (TDM) of Tac based on trough concentrations (C0) is a compromise for AUC-monitoring. The use of self-collected capillary microsamples of Tac at home will make it possible for the patients to provide 3 samples within a dosing interval without going to the hospital. Application of a limited sampling strategy (LSS) will make it clinically possible to accurately predict individual AUC:s in the clinic, using a population pharmacokinetic based computer dosing tool. This will improve Tac TDM significantly, and the aim of the present study was to evaluate the use of 3 microsampled Tac concentrations to predict individual Tac AUC:s.
*Methods: Twelve-hour Tac concentration-time profiles (13 samples) were obtained from 27 renal transplant recipients on twice-daily Tac. Blood samples were obtained using finger prick microsampling (10 μL Mitra® Neoteryx, LLC) 3 ± 1 weeks after transplantation. A non-parametric population model (Pmetrics) was used to calculate the reference AUC0-12h ref based on all 13 measured concentrations. In addition, AUC0-12 LSS were predicted from 3 samples collected at 0-, 1- and 3-hours, and AUC0-12 C0 was estimated from the single trough concentration (0-hour) with the same population model. The predictive performance of the 3-point LSS and C0 estimated AUC:s were evaluated by comparison with the reference AUC0-12h ref. Percentage relative bias was calculated.
*Results: Mean dose, trough concentration and systemic exposure of Tac (AUC0-12h ref) were 3.5 ± 1.5 mg, 6.6 ± 1.5 µg/L and 148 ± 41 µg*h/L. The 3-point prediction (AUC0-12 LSS) showed a low mean relative bias (4.2% ± 11.7). In comparison, when only using the trough concentration for prediction (AUC0-12 C0), mean relative bias was over 10 times higher; 51.1% ± 66.4.
*Conclusions: Micro sampling was patient friendly and easy to perform in a clinical practice. Using single trough concentration the predicted AUC showed too high bias for clinical application. On the other hand, taking advantage of microsampling and utilizing a 3-sample LSS method provided good predictions of individual systemic exposure of Tac, suitable for optimal individualization of Tac doses in the clinic.
To cite this abstract in AMA style:Gustavsen MT, Midtvedt K, Vethe N, Bergan S, Åsberg A. Patient Centered AUC-Monitoring of Tacrolimus Using Capillary Microsampling [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/patient-centered-auc-monitoring-of-tacrolimus-using-capillary-microsampling/. Accessed June 3, 2023.
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